The skin acts as a barrier structure in vertebrates to protect from physical, chemical, and biological insult. For example, epidermal disruption exposes antigen presenting cells resident in the skin (e.g., Langerhans cells and dendritic cells) to environmental antigens, and further stimulates keratinocytes (as the first responders of the barrier insult) to release biological signals that lead to both activation and maturation of resident immune cells. The particular immune adjuvants released by keratinocytes can direct the character of the resulting immune response, including the induction of a Th2-type response, Th17-type response, or Th1-type response. See, for example, De Bennedetto, et al., Skin Barrier Disruption—A Requirement for Allergen Sensitization, J. Invest. Dermatol. 132(3):949-963 (2012).
Improving skin barrier function and modulating the underlying immunology is important in the prevention, treatment, and management of skin conditions, including: inflammatory conditions resulting from acute or chronic chemical, environmental, and/or biological insult; hereditary defects in skin barrier function; conditions associated with aging or damaged skin; proliferative disorders involving the skin; and immunological disorders of the skin or which manifest in symptoms that affect the skin, among other conditions.
The present invention meets these and other objectives.